Comparative analysis of human mesenchymal stem cells from fetal-bone marrow, adipose tissue, and Warton's jelly as sources of cell immunomodulatory therapy
Comparative analysis of human mesenchymal stem cells from fetal-bone marrow, adipose tissue, and Warton's jelly as sources of cell immunomodulatory therapy
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DOI：
10.1080/21645515.2015.1030549
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发表时间：
2016-01-01
影响因子：
4.8
通讯作者：
Yuan, Zhengwei
中科院分区：
文献类型：
--
作者：
Wang, Qiushi;Yang, Qiaoni;Yuan, Zhengwei
鉴定不同组织间充质干细胞作为细胞免疫调节治疗的来源。检测IFN-γ对WJ-MSC的影响及其免疫调节功能特点。我们比较了人胎儿骨髓（F-BM）、脂肪组织（AT）和Warton's Jelly-derived MSCs（WJ-MSCs）的表面抗原表达、分化能力、增殖能力、克隆性、对衰老的耐受性、基因表达以及IFN-γ是否影响WJ-MSC基因表达，如通过真实的时间定量PCR所确定的。研究了15个基因。我们进一步评估了WJ-MSCs介导的对外周血单个核细胞的免疫调节作用，在以5：1的比例（PBMC：MSCs）共培养5天后，由PHA、IL-2和CD 3Ab刺激。检测WJ-MSCs对Th 1、Th 2、Th 17细胞因子分泌及Treg表达的影响。来自不同组织的MSC具有相似的细胞表面抗原表达水平和分化能力，而F-BM-MSC和WJ-MSC的细胞增殖率和克隆性高于AD-MSC。15个基因在WJ-MSCs和AD-MSCs中的表达水平相似（P > 0.05）。F-MSC中IL-6、CXCL 9、CXCL 10、CXCL 11、ICAM-1、IDO 1、HLA-G5、SDF 1A、NOTCH等9个基因表达上调，而VCAM-1表达下调。IFN-γ处理后，WJ-MSC中有7个基因上调，包括趋化因子配体CXCL 9、CXCL 10和CXCL 11，以及粘附蛋白VCAM 1和ICAM 1。此外，免疫抑制因子，如HLA-G和IDO均增加。WJ-MSCs与外周血单个核细胞共培养后，通过抑制Th 1和Th 17的增殖反应，增加Th 2和Treg的表达，发挥免疫抑制作用。IFN-γ预处理的WJ-MSCs较未预处理的WJ-MSCs能显著降低IFN-γ和TNF-α的表达，并能显著增加Treg的表达，抑制Th 17的表达（P < 0.01）。我们的研究结果表明，原始F-BM-MSCs和WJ-MSCs具有生物学优势相比，成人细胞，WJ-MSCs有一个类似的基因表达模式的AT-MSCs，但不是F-BM MSCs，和炎症刺激调节基因表达的WJ-MSCs。WJ-MSC在与PBMC共培养体系中表现出免疫抑制作用，IFN-γ可促进WJ-MSC的免疫抑制作用。
To characterize different tissue MSCs as sources of cell immunomodulatory therapy. Examined the effects of IFN-gamma on WJ-MSC and their immunomodulatory function characteristics. We compared human fetal bone marrow (F-BM), adipose tissue (AT), and Warton's Jelly-derived MSCs (WJ-MSCs) for surface antigen expression, differentiation ability, proliferation capacity, clonality, tolerance for aging, gene expression, and whether IFN-gamma affected WJ-MSC gene expression, as determined by real time quantitative PCR. Fifteen genes were examined. We further assess WJ-MSCs-mediated immunomodulatory on peripheral blood mononuclear, stimulated by PHA, IL-2 and CD3Ab after 5 days of co-cultured in a 5: 1 ratio (PBMC: MSCs). Examined the effect of WJ-MSCs on the Th1, Th2, Th17 cytokines production and Treg augument. MSCs from different tissues have similar levels of cell surface antigen expression and differentiation ability, while F-BM-MSCs and WJ-MSC had higher rates of cell proliferation and clonality than AD-MSCs. All 15 genes were expressed at similar levels in WJ-MSCs and AD-MSCs (P > 0.05). 9 genes were upregulated in WJ-MSC For F-MSC, including IL-6, CXCL9, CXCL10, CXCL11, ICAM-1, IDO1, HLA-G5, SDF1A, and NOTCH were down expression, but VCAM-1 was lower expression in WJ-MSCS. After IFN-gamma treatment, 7 genes were upregulated in WJ-MSC, including chemokine ligands CXCL9, CXCL10 and CXCL11, and the adhesion protein VCAM1 and ICAM1. Additionally, immunosuppressive factors, such as HLA-G and IDO were both increased. When cocultured with peripheral blood mononuclear, WJ-MSCs showed an immunosuppressive function by inhibit the proliferative response of Th1 and Th17 but augment Th2 and Treg. Primed WJ-MSCs by IFN gamma caused a greater reduction in IFN gamma and TNF alpha than untreated WJ-MSCs, also the effect on augument in Treg and inhibit Th17 (P < 0.01). Our results demonstrate that primitive F-BM-MSCs and WJ-MSCs have biological advantages as compared to adult cells, WJ-MSCs have a gene expression pattern similar to AT-MSCs but not F-BM MSCs, and that inflammatory stimuli regulate gene expression in WJ-MSCs. WJ-MSC showed the immunosuppressive function in co-cultured system with PBMC, and IFN gamma can promoted the immunosuppressive function.